Project: Inflammation, T Cell activation and Subclinical atherosclerosis in Treated HIV Infection

Acronym	Kenya CVHIV (Reference Number: TMA2016CDF-1598)
Duration	01/12/2018 - 30/11/2021
Project Topic	Despite the high prevalence of HIV in sub-Saharan Africa, Cardiovascular diseases (CVD) are the leading causes of morbidity and mortality in this region. Predictors of CVD are well established in resource-rich countries, but whether these same risk factors are strongly associated with CVD in sub-Saharan Africa is not known. Growing evidence from Europe suggests that HIV itself may be a risk factor for CVD, through a combination of medication side effects, inflammation and immune activation, but how HIV disease and treatment impacts CVD risk in Kenya and other countries with generalized HIV epidemics is less well studied. In addition, it remains unclear whether inflammation and immune activation truly predicts early risk of CVD in African HIVinfected subjects and should remain a target for intervention. The goal of this project is to assess the relative contributions of persistent inflammation and immune activation in subliclinical atherosclerosis in HIV-infected subjects. Our central hypothesis is that systemic immune activation and inflammation associated with HIV infection contribute to early risk of CVD in HIV positive individuals, and that CMV infection and microbial translocation may contribute to this process. Aim 1: To determine if HIV-infected individuals have increased inflammation and immune activation compare to the uninfected controls, Aim 2: To test the markers of immune activation and inflammation are associated with an increased risk of subclinical atherosclerosis. Aims 1&2 will leverage the ongoing Kenya study of cardiovascular diseases during HIV infection cohort of 300 HIV-infected on long-term antiretroviral treatment and 300 HIV-uninfected subjects. We will conduct a cross-sectional, nested case-control study of 200 HIV+ and 100 HIV- subjects and analyze banked blood from the study for markers of inflammation, CMV infection, microbial translocation and cellular immune activation, selected for their association with CVDs in HIV- uninfected populations. We will investigate associations with subclinical atherosclerosis in HIV+, adjusting for age, sex, HIV related and traditional risk factors and derive a set of candidate biomarkers to validate prospectively. This innovative and important clinical study on a well characterized cohort will illuminate the mechanisms leading to increased risk of CVD in HIV-infected individuals and provide data that will be critical to developing targeted, feasible intervention trials to combat CVD in subSaharan Africa over the next decade. It would provide a springboard for launching Dr. Temu's independent physician-scientist career in the field of HIV immunology in Kenya.
Network	EDCTP2
Call	Career Development Fellowships 2016

Project partner

Number	Name	Role	Country
1	University of Nairobi	Coordinator	Kenya